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Thematic Review |
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* Departments of Infectious Diseases, St Jude Children's Research Hospital, Memphis, Tennessee 38105
Structural Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105
Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163
1 To whom correspondence should be addressed. e-mail: charles.rock{at}stjude.org
Acyl carrier protein (ACP) is a central element in the bacterial, type II dissociated fatty acid synthase (FAS II) system. ACP delivers the fatty acyl intermediates to a variety of enzymes with different biochemical functions and 3-dimensional (3-D) structures. Computational techniques have proved invaluable in guiding the experimental designs that have uncovered the recognition helix on ACP and the common features on its target enzymes responsible for specific protein•protein interactions. Escherichia coli has been the model organism for the study of FAS II, but the availability of complete genomic sequences of a growing number of bacteria coupled with computational bioinformatics has led to new discoveries on the mechanisms that regulate E. coli FAS II and allowed the differences between the E. coli paradigm and major groups of pathogens to be identified and experimentally addressed. Computational methods facilitated the discovery of the E. coli fatty acid synthesis transcriptional regulator, FabR, and led to the identification of novel bacterial FAS II proteins in Gram-positive pathogens, including enoyl-ACP reductases (FabK and FabL) and trans-2-cis-3-decenoyl-ACP isomerase FabM.
As more genomic sequences and 3-D coordinates are added to the databases, the power and resolution of the computational approaches will increase to offer deeper insight into the structure, diversity and function of lipid metabolic pathways.
Abbreviations: ACP, acyl carrier protein; AcpM, mycobacterial ACP; AcpS, holo-ACP synthase; FAS I, type I fatty acid synthase; FAS II, type II fatty acid synthase; UFA, unsaturated fatty acid; FabA, ß-hydroxydecanoyl-ACP dehydratase/isomerase; FabB, ß-ketoacyl-ACP synthase I; FabF, ß-ketoacyl-ACP synthase II; FabG, ß-ketoacyl-ACP reductase; FabH, ß-ketoacyl-ACP synthase III; FabI, enoyl-ACP reductase I; FabK, enoyl-ACP reductase II; FabL, enoyl-ACP reductase III; FabZ, ß-hydroxyacyl-ACP dehydratase; ; FadR, fatty acid degradation regulator; and FabR, fatty acid biosynthesis reg-ulator
Supplementary key words acyl carrier protein • fatty acid synthesis • unsaturated fatty acids
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